Protein material for slow digestion and its use

ABSTRACT

The subject of the invention is the use of a protein material whose rate of digestion has been reduced, for the preparation of an enteral composition which makes it possible to modulate the postprandial plasma amino acid level, said protein material having been previously treated so as to convert the fast-digesting proteins which it contains to slow-digesting proteins, characterized in that the slow-digesting protein material is a material containing microparticulate gelled proteins combined with polysaccharides under conditions of thermodynamic incompatibility.

This application is a 371 of PCT/EP99/07909 filed Oct. 14, 1999.

BACKGROUND OF THE INVENTION

The subject of the invention is the use of protein material whose rateof digestion has been reduced, for the preparation of a compositionwhich makes it possible to modulate the postprandial plasma amino acidlevel. The subject of the invention is also a composition intended to beadministered by the enteral route to a mammal containing a proteinmaterial whose rate of digestion has been slowed down.

Because of a constant need for nutrients and the periodic nature of thediet in humans, the body has had to develop processes for storing thenutrients consumed in excess during meals and mechanisms for mobilizingthese reserves during the period of physiological starving. Thealternation of periods of food consumption and of starving areresponsible for profound modifications in the various pathways for themetabolism of nutrients.

These nychthemeral variations affect the synthesis and the degradationof proteins and consequently the protein balance. Thus, the negativeprotein balance during the period of physiological starving becomespositive during the postprandial period, a phase for assimilatingnutrients from the digestive tract. The relative importance of eachphase then determines the variation in the body protein mass. It istherefore essential to be able to improve the postprandial protein gainin order to optimize the variation in the protein mass.

The ingestion of meals consisting of proteins causes an increase in theplasma amino acid level. This rise in the availability of amino acids isassociated with a rearrangement of the various components of proteinmetabolism (protein degradation, protein synthesis, amino acidoxidation). Recently, Boirie et al. (Proc. Natl. Acad. Sci. USA, 94,14930-14935, 1997) have shown in young healthy volunteers that thepostprandial protein gain depended on the rate of digestion of theingested proteins (period between ingestion and absorption of thenutrients by the body).

Some proteins with a fast rate of digestion, such as whey proteins, canhave a high nutritive value, that is to say an adequate and balancedsupply of amino acids which are essential for the human body, such asvaline, leucine, isoleucine, phenylalanine, lysine, methionine,tryptophan and threonine. However, in spite of this good amino acidbalance, the body's use of the amino acids derived from these proteinsis not optimum, since they are digested too rapidly. Also, document WO97/05785 describes a composition used in foods for newborns whichcontains slow-digesting proteins, said proteins having been modifiedbeforehand so as to slow down the rate of digestion.

Other sources can therefore be used which contain proteins having anaturally slower rate of digestion, such as caseins, for example, butwhose amino acids supply and balance are not optimum.

The present invention aims to provide for the nutritional needs ofcertain categories of people by means of proteins whose rate ofdigestion is reduced.

SUMMARY OF THE INVENTION

The invention thus relates to the use of a slow-digesting proteinmaterial for the preparation of a composition intended to beadministered enterally to a mammal so as to modulate the postprandialplasma amino acid level, said protein material having been previouslytreated so as to convert the fast-digesting proteins which it containsto slow-digesting proteins, characterized in that the slow-digestingprotein material is a material containing microparticulate gelledproteins combined with polysaccharides under conditions of thermodynamicincompatibility.

To date, it has never been proposed to reduce the rate of digestion of aprotein with the aim of modulating the postprandial plasma amino acidlevel so as to: a) increase the postprandial protein gain; and/or b)avoid a metabolic overloading of certain organs and/or certain enzymes,and/or c) limit daily food intake by virtue of a satiating effect ofthese proteins, and/or d) compensate for certain dysfunctions in themetabolism of amino acids and more specifically for enzymaticdeficiencies, e) improve the regeneration of tissues, in particular theprocesses of wound healing.

This treatment is particularly advantageous for proteins of highnutritional value which are digested too rapidly, this being so as tooptimize the protein gain.

The subject of the invention is also a composition intended to beadministered enterally to a mammal, containing a slow-digesting proteinmaterial which has been treated beforehand so as to convert thefast-digesting proteins which it contained to slow-digesting proteins,characterized in that the slow-digesting protein material is a materialcontaining microparticulate gelled proteins combined withpolysaccharides under conditions of thermodynamic incompatibility.

The compositions thus obtained may be particularly suitable for:minimizing the losses of body proteins in elderly persons, patients whoare seriouly ill and people on a low-calorie diet; patients sufferingfrom renal or hepatic disorders; patients suffering from disfunctions inthe metabolism of amino acids such as, for example,hyperphenylalaninemia or other aminoacidopathies; patients treated withL-DOPA; and premature babies.

They may also be intended for the nutrition of pets, in particular thatof elderly subjects, the young during the period of growth and forcontrolling the body weight of some subjects.

DETAILED DESCRIPTION OF THE INVENTION

In the context of the present invention, a slow-digesting proteinmaterial is a material which, when provided in the form of a solutionand digested by 140-200 g rats, leads to a disappearance of half of theingested nitrogen present in the digestive tract in more than 80 min.

Fast protein refers to proteins which, when they are ingested in theform of a solution by 140-200 g rats, leads to a disappearance of halfof the ingested nitrogen present in the digestive tract in less than 70min.

To carry out the present invention, a protein material, that is to sayany material comprising proteins, whether they are of animal, plant ormicrobial origin, in particular proteins of milk, oil-producing plants,leguminous plants, egg or brewery yeasts, for example is used.

The materials containing proteins having a high nutritive value, basedon the recommended intakes, are particularly indicated in the context ofthe present invention. These proteins may contain a balanced and highcontent of each of the amino acids essential for the body, such aslysine, tryptophan, leucine, isoleucine, valine, phenylalanine,methionine and threonine, for example.

Preferably, the protein-containing material (untreated) comprisesfast-digesting proteins, such as for example whey proteins.

The protein-containing material is treated so that the rate of digestionof said proteins is slowed down. To this effect, the protein-containingmaterial is mixed with polysaccharides and, under conditions ofthermodynamic incompatibility, form microparticles which are gelled byheat treatment.

Indeed, biopolymers such as proteins and polysaccharides may exhibitthermodynamic incompatibility; that is to say that above a thresholdconcentration, they do not form a homogeneous mixture and separatespontaneously into two phases. One is enriched in proteins, the other isenriched in polysaccharides. At this initial stage, the separation ofthe two phases is achieved by formation of microscopic droplets, whichmay be gelled; in the case of protein droplets, a heat treatment oftenmakes it possible to form a gel. Thus, the protein microparticleformation results from a phase separation and a spontaneous gelling ofan aqueous mixture of proteins and polysaccharides (Syrbe, PhD Thesis,Techn. Univ. Munich, 1997).

The polysaccharides according to the present invention may be chosen inparticular from alginates, xanthan gum, gum arabic, guar, starch,maltodextrins and dextrins, pectins, kappa-carrageenans,iota-carrageenans, lambda-carrageenans, methyl cellulose andcarboxymethyl cellulose, sulfated dextrans and/or gellan gum.

The concentration of proteins and polysaccharides in the mixture may berespectively between 3 and 12% and between 0.2 and 1%. Theprotein/polysaccharide ratio may thus vary from 3:1 to 24:1.

The microparticles may for example be prepared from a mixture of asolution of alginate and a solution of serum proteins. The solution ofalginate is preferably at 3% and pH 7 and the solution of serum proteinsat 15%, pH 6.6. The mixture may thus be heated at a temperature ofbetween 70 and 130° C. for a period of 1-60 minutes.

The microparticles obtained have a diameter preferably of between 200 nmand 100 microns.

The conditions for treating the protein-containing material must bepreferably chosen so as to achieve a level of slowing down of the rateof digestion of said proteins such that when the treated proteinmaterial is orally administered in the form of a solution to 140-200 grats, it leads to a disappearance of half of the ingested nitrogenpresent in the digestive tract in more than 80 min, for example.

The protein material thus treated may be advantageously used for thepreparation of a food or pharmaceutical composition intended to beorally administered to a mammal so as to: 1) increase the postprandialprotein gain, and/or 2) avoid a metabolic overloading of certain organsand/or certain enzymes, and/or 3) limit daily food intake by virtue of asatiating effect of these proteins, and/or 4) compensate for certaindysfunctions in the metabolism of amino acids and more specifically forenzymatic deficiencies, and/or 5) improve the efficacy of treatmentswith L-DOPA, 6) improve the regeneration of tissues, in particular theprocesses of wound healing.

The present use is however not limited to a protein material treated asdescribed above. Indeed, other treatments may also induce a reduction inthe rate of digestion of a protein-containing material. The present useis therefore intended to also use any protein material which has beentreated beforehand so as to convert the fast-digesting proteins which itcontained to slow-digesting proteins.

Thus, certain technological modifications, such as the thermal gelling,the mixing of these proteins with polysaccharides which can gel in thestomach, the formation of gelled microparticles as well as thepreliminary supply of casomorphines in the form of a casein hydrolysatecan make the rate of digestion of proteins slower.

It is possible, for example, to use one of the materials containingproteins which is cited above, combined with anionic polysaccharides.

The slow-digesting protein material is capable of improving orpreventing problems linked with various physiological orphysiopathological states. Indeed, the protein materials with a slowrate of digestion can act according to 4 principal modalities: byoptimizing the postprandial protein gain, by avoiding excessivefunctioning for key organs or for certain enzymes, by optimizingtreatments with L-DOPA and by increasing the sensation of satiety. Theconditions governing the use of these proteins will depend in particularon the categories of people concerned.

In the context of the optimization of the postprandial protein gain,cases of undernourishment may be treated. Undernourishment frequentlyexists in elderly subjects or during diseases which comprise asubstantial loss of body proteins—renal insufficiency, severe burns,trauma, surgical or infectious stress, inflammation, cancer or AIDS.This metabolic state manifests itself by a negative nitrogen balancewhich is the consequence of a fusion of the body, and more particularlymuscle, proteins. Indeed, the muscle proteins are degraded so as toprovide energy to the body and allow the redistribution of the aminoacids to the synthesis of specific proteins.

In cases of undernourishment, the ingestion of slow-digesting proteinmaterial is capable of limiting this protein loss, by optimizing thepostprandial protein gain. This protein material ought to increase therate of physiological recovery, resistance to attacks, the quality oflife and therefore the vital prognosis.

Renal abnormality, in the broad sense of the term, is an example of theuse of the slow-digesting protein material which is not solely based onthe optimization of the postprandial protein gain, although it is anessential component thereof. Indeed, during renal abnormalities,patients are subjected to a strict hypoprotein diet so as to reduce theproduction of nitrogenous waste. It is commonly accepted that such adiet has a favorable effect on the general condition, the quality oflife and even on the renal function. However, this diet is very poorlytolerated by patients. The ingestion of slow-digesting protein materialcontributes toward:

1) reducing the production of nitrogen which should be subsequentlyeliminated by the kidneys;

2) distributing this production over a much longer period; and

3) increasing the satiating action of this type of protein in order toensure better tolerance of the diet. Proteins with a slow rate ofdigestion are consequently particularly suitable for the nutrition ofpatients with renal disorders.

Likewise, the slow-digesting protein material may be prescribed forpatients with pathological hepatic conditions. After a meal composed ofvarious nitrogenous compounds (proteins, peptides, amino acids), theliver will try to maintain the amino acid concentration withinphysiological limits by breaking down a portion of the amino acidsderived from the diet. A moderate arrival of dietary amino acids iscapable of reducing the excessive activity of an organ which exhibitspathological conditions and which will consequently make it possible toavoid excessive work. In addition, the slow-digesting protein materialinduces a better postprandial protein gain.

During a deficiency in proteolytic pancreatic enzymes, the ingestion ofslow-digesting protein material can contribute toward improving thedigestion process. This benefit is brought about by the reduction in thequantity of substrate to be hydrolyzed by the proteolytic enzymes of thepancreas and therefore by the obtaining of a better enzyme/substrateratio. Furthermore, with the slow-digesting protein material, there is abetter postprandial protein gain.

In diseases where dysfunctions exist in the metabolism of amino acidsand more specifically enzyme deficiencies in the pathway of degradationof these amino acids (phenylalaninemia and phenylketonuria,hypertyrosinemia, histidinemia, homocystinuria, amino acidopathieslinked to branched amino acids, for example), the accumulation of theseamino acids or of one of their degradation products producesneurological and clinical complications. To avoid this accumulation, adietetic treatment is prescribed. It consists of a diet which does notcontain—or contains a very small quantity of—the amino acid implicatedin the development of the disease. The specific products developed forthese populations are composed either of free amino acids, or of highlyhydrolyzed proteins. However, these mixtures do not possess a pleasanttaste. Furthermore, to avoid diarrhea following on from thehyperosmolarity of the products, consumers should ingest the products inthe form of small meals. The protein material which possesses both aslow rate of digestion and a small content of the implicated amino acid,makes it possible to improve the taste and therefore the tolerance ofthe diet, to limit the risk of diarrhea, to avoid plasma fluctuations inamino acids, and to increase the postprandial protein gain.

The use of slow-digesting protein material can also be envisaged forpeople who are not undernourished, such as premature babies, newborns,children, obese individuals and elderly persons, for example.

The ingestion of slow-digesting protein material, in premature babies,newborns or children who are not undernourished, by providing a betteryield of use of the dietary proteins, is capable of promoting bodygrowth.

The slow-digesting protein material, by reducing the food intake by asatiating mechanism, may be administered to people with disorders ofweight homeostatis (obesity) or during episodes of bulimia. It can limitthe reduction in the protein mass subsequent to being on a low-caloricdiet. These two combined factors make it possible to reduce their fattymass with, on the one hand, greater ease for reducing their suppliesand, on the other hand, a better preservation of their protein mass.

In elderly persons, compared with young subjects, there is a reductionin the body protein mass, a reduction which has an influence on theautonomy, the resistance to attacks (diseases, various stresses) and theability to recover from these attacks. Furthermore, aging is associatedwith a reduction in renal activity. The slow-digesting protein material,by therefore allowing better preservation of the protein mass, thusmakes it possible to avoid renal excesses.

The protein material with a slowed rate of digestion, by providing theamino acids in a more continuous and regular manner, makes it possibleto promote the synthesis of novel tissue materials which are involved inthe processes of wound healing or of regeneration of biological tissues.

The protein material with a slowed rate of digestion may be intended forthe nutrition of pets, in particular that of elderly subjects and theyoung in the growth phase. It can also be administered to certainsubjects so as to control their body weight.

The proteins contained in the compositions according to the inventioncan provide from 5 to 100% of the total energy, in particular from 8 to30%, and preferably from 10 to 20%. In the case of the compositionsintended for use as pet food, the protein content may be up to 40% onthe basis of the dry extract.

These compositions preferably comprise a source of carbohydratesproviding 0 to 70% of the total energy. The carbohydrates are importantnutrients for re-establishing the energy balance. All carbohydrates canbe used, in particular maltodextrins, sucrose, lactose and glucose, forexample.

The compositions may comprise a source of lipids which provide up to 35%of the total energy. Vegetable oils are recommended, in particular thoseof soybean, oil palm, coconut, sunflower and the like. In the case ofthe compositions intended for use as pet food, the source of lipids canprovide up to 60% of the total energy.

The energy value of these compositions may be between 70 and 200Kcal/100 ml, for example.

In the case of the compositions intended for infant nutrition, theproteins preferably represent 0.45 to 0.7 g/100 kJ, the carbohydratespreferably 1.7-3.4 g/100 kJ and the lipids preferably 0.1-1.5 g/100 kJ.

In the case of compositions intended for patients suffering fromphenylketonurea, the protein material may contain about 50% ofcaseinoglycomacropeptides, a source of carbohydrates, a source of lipidsand vitamins and minerals.

The compositions according to the present invention may be prepared inall sorts of ways, the steps of manufacture generally including adispersion of the ingredients in water, emulsification andpasteurization.

The compositions may be prepared in the form of liquid or semisolidconcentrates or drinks or in the form of a powder which may bereconstituted in water, for example. They may also be provided in asolid form, such as cereals, nutritional bars, for example.

Minerals, vitamins, salts, emulsifiers or flavoring compounds may alsobe added to the compositions, as required. The vitamins and minerals mayrepresent from 25 to 250% of the recommended daily supplies. In the caseof infant formulas, the quantities of vitamins and minerals prescribedby the European Directive are added.

The present invention is described in greater detail below with the aidof the examples which are given by way of illustration of the subject ofthe invention and do not constitute in any manner a limitation thereto.The percentages are given by weight unless otherwise stated. Theseexamples are preceded by a brief description of the figures.

FIG. 1: presents the percentage of proteins hydrolyzed as a function oftime for the in vitro digestion of native whey, native whey+alginate andmicroparticulate whey+alginate.

FIG. 2: represents the percentage of nitrogen ingested and remaining inthe digestive tract (stomach+small intestine) as a function of timeduring the digestion in vivo of solutions of native whey, nativewhey+alginate or microparticulate whey+alginate.

FIG. 3: represents the percentage of nitrogen ingested and remaining inthe digestive tract (stomach+small intestine) as a function of timeduring the digestion in vivo of complete meals containing proteins ofnative whey ( ) or of modified whey+alginate (•).

FIG. 4: represents the curves for “hunger”, “desire to eat” and“distension of the stomach” for meals based on proteins of native whey(NW) and modified whey (MW) as a function of time.

EXAMPLE 1 Kinetics of Digestion of Protein Solutions

The microparticles of whey are prepared from a mixture of 3% alginatesolution (Manucol DM, Kelco) at pH 7 and a 15% solution of serumproteins (Lacprodan DI-9223; Danmark Protein) whose pH is 6.6.

The concentrations in the mixture are 1% of alginate and 10% ofproteins. The mixture is heated at 80° C. for 10 minutes and will bediluted two-fold so as to obtain a final protein concentration of 5%.The microparticles have a diameter between 500 nm and 5 microns.

The enzymatic hydrolysis in vitro and in vivo of the microparticles iscompared with that of a 5% solution of native proteins and with that ofa mixture of native proteins (5%) and of alginate (0.5%).

The enzymatic digestion in vitro is carried out according to the methoddescribed by Savalle et al. (J. Agric. Food Chem., 37, 1336, 1989) andmodified in the following manner: the samples, containing 250 mg ofproteins, are incubated at 37° C. in the presence of pepsin (1 mg) at pH1.9 for 30 minutes. The medium is then neutralized at pH 7.5 with sodiumhydroxide and digestion with pancreatin is carried out for 5 h 30 min.The degree of hydrolysis is determined by measuring the free aminogroups by the TNBS method (Adler-Nissen, J. Agric. Food Chem, 27, 1256,1979). Before incubation, the samples were ground by passing through asyringe 1 mm in diameter so as to simulate in vitro the conditions ofgavage which are used in vivo in rats.

The kinetics of hydrolysis in vitro is represented in FIG. 1. Theresults show that the microparticulate whey is digested more slowly thanthe native whey containing alginate or not, this being more particularlyduring the first two hours of hydrolysis.

In vitro, the native whey is only about 30% hydrolyzed (the value 100%of proteins not hydrolyzed plotted on the graph corresponds to thequantity of NH₂ groups contained in the whey, according toAdler-Nissen).

For the study of digestion in vivo, 21 male Sprague-Dawley rats(Iffa-Credo, F-6210 L'Arbresle, France), weighing 160 to 180 g, arerandomly distributed into 11 groups. After a period of acclimatizationof at least 2 days, the animals are placed in metabolic cages (to avoidcoprophagy) and starved for 22 hours. The rats are then fed by gavagewith a suspension of 5 ml of test protein at 5%.

The rats are anesthetized at 0, 10, 20, 30, 60, 90, 120, 180, 240, 360minutes after gavage. The abdominal cavity is opened and blood samplesare taken from the portal vein and the dorsal aorta. The animals arethen sacrificed; the stomach and the small intestine are separated fromthe abdominal cavity. The gastric and intestinal contents are recoveredby washing the luminal content with a 0.9% NaCl solution.

The blood samples are mixed with heparin and centrifuged. The plasmasamples are deproteinized with sulfosalicylic acid at 3.6% (w/v, finalconcentration) and then stored at −80° C. up to the analysis of theamino acids (amino acid analyzer, system 6300-Beckman).

The gastrointestinal contents are kept at low temperature and theirtotal nitrogen content is rapidly analyzed.

The percentage of nitrogen ingested and remaining in the digestive tract(stomach+small intestine) as a function of time is represented in FIG.2.

The results show that in solution, the microparticulate whey is digestedless quickly than the native whey, and that this effect is due to themodification and not to the presence of alginate. The disappearance ofhalf of the ingested nitrogen from the digestive tract occurs after 90min for the microparticulate whey whereas it occurs after 45 minutes forthe native whey.

EXAMPLE 2 Kinetics of Digestion of the Proteins Contained in CompleteMeals

The procedure is carried out as described in Example 1, the differencebeing that the rats are force-fed with a complete meal of the followingcomposition (% by weight): 5% of proteins of native or microparticulatewhey, 8% of soybean oil, 0.1% of emulsifier, 17% of sucrose, 8% ofmaltodextrins and 61.9% of water.

The results presented in FIG. 3 indicate that in a complete meal, theprotein whose rate of digestion has been slowed down is more slowlydigested than the native protein. The disappearance of half of theingested nitrogen from the digestive tract occurs after 145 minutes forthe microparticulate whey whereas it occurs after 78 minutes for thenative whey.

EXAMPLE 3 Study of Satiety in Human Volunteers

Materials and methods

Samples:

The isolate of whey proteins (NW) was provided by MD-Foods. The proteinsolutions for drinking were prepared by mixing the ingredients given inTable 1 in dimineralized water, and then left overnight at 4° C., withstirring.

The proteins of microparticulate whey (MW) were prepared from NWaccording to the following steps:

1) dissolve the alginate and the remainder of the ingredients separatelyin water.

2) Mix the 2 solutions so as to obtain the final composition given inTable 1, and distribute the composition into stainless steel dishes of200 g each, sealed and then heated in an oven at a temperature of 105°C. until the internal temperature reaches 78° C., and then cooled.

3) The drinks and the gel of whey proteins are flavored, sweetened andcolored to enhance their palatability. Flavorings of different sorts andat different concentrations were tested by a panel of 8 people and theproducts and doses most frequently chosen were used for the finalcompositions (Table 1).

The meals (400 g) have isoenergy levels (178 Kcal/portion) andisoprotein levels (40 g/portion).

TABLE 1 Composition of the protein meals (in g per portion of 400 g) NWMW Isolate of whey proteins 47.6 47.6 Sodium alginate 2.0 Artificialsweetener 1.6 1.6 Sucrose 8.0 8.0 Caramel flavor 0.8 0.8 Caramelcoloring 0.02 0.02 Water 342.0 340.0

Subjects

5 human volunteers having an average age of 32.5±6.9 and a mean bodymass index of 22.3±1.7 Kg/m², received one of the 2 meals on each of the2 days of the experiment.

Protocol

The subjects did not consume any alcoholic drinks on the day before thestudy and had a light dinner before 8 pm and fasted up to the beginningof the protocol. 3 meals were consumed on the day of the protocol:

1) A light and standard breakfast consisting of a slice of wholemealbread, 5 g of butter, 10 g of jam and coffee or tea with milk (150Kcal). It was served at 7.45 am and was consumed in 10-15 min.

2) The test meals were served at 10 am and consumed in about 15 minutes.

3) A meal based on pasta with tomato sauce and kiwis was served at 1 pm.

The volunteers noted their sensation of hunger, feeling hungry anddistension of the stomach, on a visual analog scale (10 cm) at 30 minuteintervals between 10 am and 1 pm.

During the 1 pm meal, where the volunteers ate until they were full, thequantity of pasta and tomato sauce ingested was checked and weighed. Thequantity of kiwis consumed was checked per unit (100±5 g per unit). Thesubjects noted in a notebook the foods consumed during the rest of theday of the study. The quantity of the various foods consumed duringlunch and the rest of the day made it possible to estimate the number ofKcal ingested, using the food composition table by McCance and Widdowson(1991).

Results

The curves for “hunger”, “feeling hungry” and “distension of thestomach” are given in FIG. 4. The proteins of native whey (NW) andmodified whey (MW) behave differently. The return of hunger and of thedesire to eat is slower with the meal based on MW and the sensation ofdistension of the stomach lasts longer for MW.

The mean calorie supply during the meal and during the rest of the daywas compared after a first load of NW and MW. The results in Table 2show that in the case of MW, this supply is reduced.

The results show a more hunger-satisfying effect of modified wheycompared with native whey.

TABLE 2 Calorie supply in Kcal NW MW Meal 1459 ± 772 1091 ± 333 Rest ofthe day  933 ± 273  731 ± 262 Meal + rest of the day 2392 ± 682 1822 ±547

EXAMPLE 4 Study of the Nutritional Quality of the Modified Protein

Materials and methods

The proteins of microparticulate whey MW were prepared by mixing asolution of alginate at 2% by weight and 20% by weight of a solution ofwhey proteins in a 1:1 ratio. The composition is distributed into 200 mldishes and then treated as described in Example 2.

Two diets are prepared by mixing, in a mixer, the ingredients presentedin Table 3. They are given for 21 days to 2 batches of 10 maleSprague-Dawley rats weighing about 60 g at the beginning of the study.The variation in weight, as well as the quantity of diet food ingestedduring the 3 weeks are measured. In the second week of the study, theanimals are transferred in metabolic cages and the feces and urine arecollected for 7 days.

TABLE 3 Composition of the diets NW diet MW diet Whey proteins 5.9725.972 Vitamins 0.500 0.500 Minerals 1.750 1.750 Choline bitartr. 0.1000.100 Cellulose 2.500 2.500 Soybean oil 5.000 5.000 Maltodextrin 34.17833.678 Alginate 0.500 Water 50.000 50.000 TOTAL 100.000 100.000 NW:proteins of native whey, MW: proteins of modified whey

The following parameters were then measured:

digestibility (D),

biological value (BV),

net protein use (NPU),

protein efficacy ratio (PER)

The results given in Table 4 show a slight decrease in the digestibilityof nitrogen in the case of an MW diet, which has no effect on the netprotein use (NPU) by virtue of a slightly improved absorbed nitrogen use(BV). The protein efficacy ratio is moreover not affected by thetreatment (PER).

The results show that the protein microparticle formation does notadversely affect its nutritional quality.

TABLE 4 PER; digestibility, BV and NPU for rats fed with NW diet and MWdiet for 21 days (mean ± 95% confidence interval). PER Digestibility BVNPU NW 3.38 ± 0.11 97.6 ± 0.3 68.7 ± 6.7 67.0 ± 4.7 MW 3.30 ± 0.18 95.6± 0.4 (*) 73.1 ± 4.1 69.9 ± 2.8 (*) Significantly different from p <0.05

EXAMPLE 5 Food Composition for Unweaned Babies

A food composition for unweaned babies is prepared in the form of asoluble powder having the composition defined in Table 5 below. Thispowder is used at the rate of 13% in water, which corresponds to anenergy density of the order of 70 kcal/100 ml.

To prepare this powder, water is purified by reverse osmosis, it isheated to 70° C., a source of proteins and a source of carbohydrates areadded to it, a source of lipids in which fat-soluble vitamins have beendispersed beforehand is added to it, the mixture is heated at 80° C. for5 min by injection of steam, it is cooled to 60° C. and minerals andwater-soluble vitamins are added to it, it is homogenized in 2 stages at10 mPa and then at 7 mPa, it is spray-dried under a hot air stream to awater content of 4%, and then it is reduced to a fine powder which issoluble in water.

Vitamins and minerals are added to the composition in a quantitysatisfying the recommended daily intakes.

TABLE 5 PROTEINS 2.3 g/100 Kcal Casein  40% Whey treated according toExample 1  60% CARBOHYDRATES  10 g/100 Kcal Lactose 100% LIPIDS 5.5g/100 Kcal Milk fat  70% Canola oil  15% Corn oil  14% Soybean lecithin 1%

EXAMPLE 6 Enteral Composition

A liquid enteral composition containing the ingredients defined in Table6 below is prepared in the same manner as in Example 5, the differencebeing that the mixture is homogenized at 150° C. by injection of steam,it is cooled to 75° C. and it is aseptically packaged in containers.Vitamins and minerals are added to it in a quantity satisfying therecommended daily intakes.

This composition has an energy density of 100 Kcal/100 ml.

TABLE 6 PROTEINS  6.5 g/100 ml Whey treated according to Example 1  100%CARBOHYDRATES 11.3 g/100 ml Solids of a corn syrup   56% Sucrose 34.4%Xanthan  9.6% LIPIDS  3.4 g/100 ml Coconut oil   50% Canola oil   30%Corn oil   14% Soybean lecithin   6%

EXAMPLE 7 Nutritional Supplement for Patients Suffering from RenalInsufficiency

A liquid composition intended for people suffering from renalinsufficiency, containing the ingredients defined in Table 7 below, isprepared in the same manner as in Example 6. Vitamins and minerals areadded in a quantity satisfying the recommended daily intakes.

This composition has an energy density of 200 Kcal/100 ml.

TABLE 7 PROTEINS  5 g/100 ml Whey treated according to Example 1  100%CARBOHYDRATES 27 g/100 ml Solids of a corn syrup   56% Maltodextrin34.4% Sucrose  9.6% LIPIDS  8 g/100 ml Coconut oil   50% Canola oil  30% Corn oil   14% Soybean lecithin   6%

EXAMPLE 8 Food Composition for Patients Suffering from Phenylketonuria

A food composition for phenylketonurics is prepared in the same manneras in Example 5, in the form of a soluble powder and having thecomposition defined in Table 8 below. Vitamins and minerals are added ina quantity sufficient for the recommended daily intakes.

This powder is used at the rate of 15% in water, which corresponds to anenergy density of the order of 70 kcal/100 ml and to a phenylalaninecontent of the order of 10 mg/100 ml.

TABLE 8 PROTEINS 3.3 g/100 Kcal Caseinoglycomacropeptide treatedaccording to  50% Example 1 Free amino acids  50% L-Arginine, L-Cystine,L-Glutamine, L-Glycine L-Histidine, L-Isoleucine, L-Leucine, L-Lysine,L-Methionine, L-Proline, L-Tryptophan, L-Tyrosine, L-ValineCARBOHYDRATES  13 g/100 Kcal Lactose 100% LIPIDS 3.9 g/100 Kcal Canolaoil  60% Corn oil  39% Soybean lecithin  1%

EXAMPLE 9 Low-calorie Nutritional Supplement

A nutritional composition intended for people wishing to reduce ormaintain their weight is prepared in the form of a soluble powder,flavored with chocolate and having the composition defined in Table 9below. Vitamins and minerals are added in a quantity satisfying therecommended daily intakes.

This powder is used at the rate of 13% in skimmed milk, whichcorresponds to an energy density of the order of 100 kcal/100 ml.

To prepare this powder, all the ingredients are mixed in the dry state,the mixture is conditioned by wetting and drying again to a watercontent of 4%, then the mixture is reduced to a fine powder which issoluble in water.

TABLE 9 PROTEINS 35 g/100 g Whey treated according to Example 1 100%CARBOHYDRATES 63 g/100 g Sucrose 65% Maltodextrin 10% Cellulose 25%

EXAMPLE 10 Flavored Composition for Elderly Persons

A liquid nutritional composition, intended for elderly persons, flavoredwith strawberry and having the composition defined in Table 10 below, isprepared as described in Example 6. Vitamins and minerals are added in aquantity satisfying the recommended daily intakes.

TABLE 10 COMPOSITION INGREDIENTS (g/100 g) Sucrose 6.0750 Maltodextrins4.8830 Proteins 7.5000 Rapeseed oil 1.3550 Corn oil 0.4670 Corn starch0.4070 Strawberry flavor 0.1960 Monoglycerides 0.1830 Vitamin C 0.0324Dibasic Na phosphate 0.0249 Iota caraageenans 0.0247 Micronutrients0.0187 Choline chloride 0.0183 Minerals: 0.2704 K, Fe, Zn, Mg Coloring0.0020 Water 78.566 TOTAL 100.0000 Calories/g 1.00

EXAMPLE 11 Composition for Use as Pet Food

Three variants of a highly palatable meat-based cat food are prepared towhich premixes of minerals and vitamins, as well as taurine are added.The whole is gelled either by addition of guar gum at 0.3% (variant A),or by addition of xanthan gum at 0.5% (variant B). The guar gum and thexanthan gum are added after wetting. However, variant B containingxanthan gum is then finely ground by means of a rotary apparatusincorporating a grid. The third variant (variant C) is identical tovariant A, but it is treated by finely grinding in the same manner asvariant B containing xanthan gum. The variants are then packaged inboxes with a capacity of 156 g and then sterilized in industrialautoclaves. Although the palatability remains similar between the 3variables, the xanthan gum contributes to a texture which is markedlydifferent from that of the other variants.

The nutritional composition of the variants is indicated below:

Carbo- Mois- Proteins Fat Fibers Ash hydrates ture (%) (g/100 g) (g/100g) (%) (%) (%) Vari-ant 79.4 12.9 5.2 0.14 1.65 0.65 A Vari-ant 79.812.5 5.3 0.10 1.41 0.82 B Vari-ant 79.4 12.8 5.1 0.11 1.88 0.70 C

A group of 36 adult cats consumed a food similar to the control diet forone week, and was then separated into 3 groups of 12 cats each consumingeither variant A, variant B, or variant C, for 13 days. At the end ofthe 13 days, the treatments were switched for another 13 days. Thus,each cat received two variants, each for 13 days, according to an openblock crossover experimental design.

At the end of the test, it was observed that some cats had soft feces.This was therefore taken into account in the interpretation of theresults.

During the first phase of the study, it was observed that the catsreceiving variable B lost more weight in a statistically significantmanner at p=0.05 than for the other variants, in spite of similar foodintakes. This effect was maintained when the results for the cats whichhad soft feces were excluded from the analysis, the difference in weightloss between variants A and B remaining statistically significant.

Variation in weight Food intake (% of the initial weight) (g/day.cat)All cats Soft feces excluded Variant A 41.1 ± 11.9 −0.11 ± 2.76 +0.03 ±2.85 Variant B 41.7 ± 12.7 −4.01 ± 2.52 −3.22 ± 1.78 Variant C 43.4 ±11.2 −1.81 ± 2.56 −1.88 ± 2.75

This result indeed shows the benefit of the present invention forcontrolling the body weight in pets.

EXAMPLE 12 Food for Puppies

A complete extruded food for puppies was prepared based on cereals andsources of proteins. Its nutritional composition is the following:proteins at least 22%, lipids at least 8%, fiber 4.5% approximately,moisture 12% at most, calcium at least 1%, phosphorus at least 0.8%. Theaddition of xanthan gum to the composition by appropriate means makes itpossible to obtain beneficial effects on the growth of the puppies.

EXAMPLE 13

Extruded food as described in Example 12, in which the content of lipidsis at least 5% but less than 8%. The addition of xanthan gum to thecomposition by appropriate means makes it possible to help to limitbodyweight gain in dogs.

What is claimed is:
 1. A method for modulating the postprandial plasmaamino acid levels in a mammal comprising the step of administering to amammal a composition including a slow-digesting protein, theslow-digesting protein being a protein material containingmicroparticulate gelled proteins that are combined with polysaccharidesunder conditions of thermodynamic incompatibility, the protein materialhaving been treated so as to convert any fast-digesting proteins whichthe protein material contains to slow-digesting proteins.
 2. The methodof claim 1 wherein the composition modulates the postprandial plasmaamino acid levels by increasing a postprandial protein gain in themammal.
 3. The method of claim 1 wherein the composition modulates thepostprandial plasma amino acid levels by avoiding a metabolicoverloading of certain organs in the mammal.
 4. The method of claim 1wherein the composition modulates the postprandial plasma amino acidlevels by avoiding a metabolic overload of certain enzymes in themammal.
 5. The method of claim 1 wherein the composition modulates thepostprandial plasma amino acid levels by limiting daily food intake inthe mammal by virtue of a satiating effect of these proteins.
 6. Themethod of claim 1 wherein the composition modulates the postprandialplasma amino acid levels by compensating for certain dysfunctions in themetabolism of amino acids in the mammal.
 7. The method of claim 1wherein the composition modulates the postprandial plasma amino acidlevels by improving the regeneration of tissues in the mammal.
 8. Themethod of claim 1 wherein the mammal is a human suffering from renalinsufficiency.
 9. The method of claim 1 wherein the mammal is a humansuffering from hepatic pathologies.
 10. The method of claim 1 whereinthe mammal is a human suffering from dysfunctions in the metabolism ofat least certain amino acids.
 11. The method of claim 1 wherein themammal is a pet.
 12. The method of claim 11 wherein the pet is elderly.13. The method of claim 11 wherein the pet is in a period of growth. 14.The method of claim 1 wherein the protein material is gelled by heattreatment.
 15. The method of claim 1 wherein the polysaccharides arechosen from the group consisting of: alginates; xanthan gum; gum arabic;guar; starch; maltodextrin and dextrins; pectins; kappa-carrageenans;iota-carrageenans; lambda-carrageenans; methyl cellulose andcarboxymethyl cellulose; sulfated dextrans; and gellan gum.
 16. Acomposition intended to be enterally administered to a mammal containinga slow-digesting protein material containing microparticulate gelledproteins combined with polysaccharides under conditions of thermodynamicincompatibility.
 17. The composition of claim 16, wherein thepolysaccharides are chosen from the group consisting of: alginates;xanthan gum; gum arabic; guar; starch; maltodextrin and dextrins;pectins; kappa-carrageenans; iota-carrageenans; lambda-carrageenans;methyl cellulose and carboxymethyl cellulose; sulfated dextrans; andgellan gum.
 18. The composition of claim 16 wherein the proteins aregelled by heat treatment.
 19. The composition of claim 16 comprising: asource of proteins providing at least 8% of the total energy; a sourceof carbohydrates providing up to 70% of the total energy; and a sourceof lipids providing up to 35% of the total energy.
 20. The compositionof claim 16 having an energy density of between approximately 70 toabout 200 Kcal/100 ml.
 21. The composition of claim 16 wherein theprotein material contains about 50% by caloric content ofcaseinoglycomacropeptides.
 22. The composition of claim 21 including asource of carbohydrates, a source of lipids, and vitamins and minerals.23. The composition of claim 16 wherein the composition is in the formof a pet food.
 24. The composition of claim 23 in which the source oflipids represents up to 60% of the total energy and the quantity ofproteins up to 40% on the basis of the dry extract.
 25. A compositionintended to be enterally administered to a mammal containing aslow-digesting protein material, the slow-digesting protein materialhaving been previously treated so as to convert fast-digesting proteinswhich the slow-digesting protein material contained to slow-digestingproteins.
 26. The composition of claim 25 wherein the slow-digestingprotein material includes particulate gelled proteins combined withpolysaccharides under conditions of thermodynamic incompatibility. 27.The composition of claim 25 wherein the polysaccharides are chosen fromthe group consisting of: alginates; xanthan gum; gum arabic; guar;starch; maltodextrin and dextrins; pectins; kappa-carrageenans;iota-carrageenans; lambda-carrageenans; methyl cellulose andcarboxymethyl cellulose; sulfated dextrans; and gellan gum.
 28. Thecomposition of claim 25 comprising: a source of proteins providing atleast 8% of the total energy; a source of carbohydrates providing up to70% of the total energy; and a source of lipids providing up to 35% ofthe total energy.
 29. The composition of claim 25 having an energydensity of between approximately 70 to about 200 Kcal/100 ml.
 30. Thecomposition of claim 25 wherein the slow-digesting protein materialcontains about 50% by caloric content of caseinoglycomacropeptides. 31.The composition of claim 30 including a source of carbohydrates, asource of lipids, and vitamins and minerals.
 32. The composition ofclaim 25 wherein the composition is in the form of a pet food.
 33. Thecomposition of claim 32 in which the source of lipids represents up to60% of the total energy and the quantity of proteins up to 40% on thebasis of the dry extract.